卢修斯（Lucius）比美替尼（Lucibinim/Binimetinib）英文说明书

Lucius (Lucibinim/Binimetinib) English Prescribing Information

1. DRUG DESCRIPTION
Generic Name: Binimetinib
Brand Name: Lucibinim®
Dosage Form: Film-coated tablets (15 mg)
Pharmacological Class: MEK1/2 inhibitor
Manufacturer: Lucius Pharmaceuticals

2. MECHANISM OF ACTION
Binimetinib is a reversible, selective inhibitor of MEK1 and MEK2, key components of the MAPK signaling pathway (RAS-RAF-MEK-ERK). By inhibiting MEK phosphorylation and activation, it suppresses tumor cell proliferation and survival in BRAF-mutated cancers.

3. INDICATIONS AND USAGE
Lucibinim® is indicated in combination with encorafenib for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test.

4. DOSAGE AND ADMINISTRATION

• Recommended dosage: 45 mg (three 15 mg tablets) orally twice daily (approximately every 12 hours) in combination with encorafenib 450 mg once daily

• Treatment duration: Until disease progression or unacceptable toxicity

• Administration: May be taken with or without food. Swallow tablets whole with water.

5. DOSAGE MODIFICATIONS
Dose reduction schedule:

• First reduction: 30 mg (two tablets) twice daily

• Second reduction: 15 mg (one tablet) twice daily

• Permanently discontinue if unable to tolerate 15 mg twice daily

6. CONTRAINDICATIONS

• Hypersensitivity to binimetinib or any excipients

• Concurrent use with strong CYP3A4 inducers

7. WARNINGS AND PRECAUTIONS

• Cardiomyopathy: Assess LVEF before treatment, after 1 month, then every 2-3 months

• Venous thromboembolism: Monitor for signs of DVT and PE

• Ocular toxicity: Perform ophthalmologic evaluation for visual disturbances

• Interstitial lung disease: Monitor for new or progressive pulmonary symptoms

• Hepatotoxicity: Monitor liver enzymes periodically

• Rhabdomyolysis: Monitor CPK levels regularly

• Embryo-fetal toxicity: Can cause fetal harm; advise effective contraception

8. ADVERSE REACTIONS
Most common adverse reactions (≥20%):

• Fatigue

• Nausea

• Diarrhea

• Vomiting

• Abdominal pain

• Arthralgia

• Myalgia

• Visual impairment

• Rash

9. DRUG INTERACTIONS

• Strong CYP3A4 inhibitors: May increase encorafenib exposure

• Strong CYP3A4 inducers: May decrease encorafenib exposure

• Acid-reducing agents: May decrease binimetinib absorption

10. USE IN SPECIFIC POPULATIONS

• Pregnancy: Category D - positive evidence of risk

• Lactation: Advise not to breastfeed

• Pediatric use: Safety not established

• Hepatic impairment: Use caution in severe impairment

• Renal impairment: No dose adjustment needed

11. CLINICAL PHARMACOLOGY

• Peak plasma concentration: 1.6 hours

• Protein binding: 97%

• Elimination half-life: 3.5 hours

• Metabolism: Primarily via UGT1A1-mediated glucuronidation

• Excretion: Feces (62%), urine (31%)

12. CLINICAL STUDIES
The COLUMBUS trial demonstrated:

• Median PFS: 14.9 months (combination) vs 7.3 months (vemurafenib)

• ORR: 63% (combination) vs 40% (vemurafenib)

• Median DOR: 16.6 months (combination)

13. STORAGE AND HANDLING

• Store at 20-25°C (68-77°F)

• Protect from moisture

• Keep in original container

14. PATIENT COUNSELING INFORMATION

• Take exactly as prescribed

• Report any visual changes immediately

• Use effective contraception

• Avoid grapefruit products

• Do not take missed doses; resume next scheduled dose

15. HOW SUPPLIED

• NDC: [Insert NDC number]

• Packaging: Bottles of 180 tablets (15 mg)

Rx only

Please refer to full prescribing information for complete details.

Manufactured by:
Lucius Pharmaceuticals
[Company Address]